1. Field of the Invention
The present invention relates to an RNA interference technology, particularly to a specific GRP78 expression-inhibition RNAi sequence, a medicine thereof and a method thereof.
2. Description of the Related Art
The 78-kDA glucose regulated protein (GRP78), also known as hsp70-5, hspA5 or Bip, is one member of the heat shock protein 70 (HSP70) family. GRP78 is a functional protein, which implements folding up a newly-synthesized protein to have an appropriate conformation in endoplasmic reticulum. According to previous researches, a crisis of cells, such as a hypoxia state or an ultraviolet radiation, will trigger GRP78 to assist in the degradation of the incorrectly folded protein. Therefore, GRP78 is thought to be a stress sensor of endoplasmic reticulum, which functions as the cyto-protection and anti-apoptosis mechanisms of cells.
It is also found in some researches that GRP78 can function as the labeled protein of breast cancer. GRP78 can help cells survive in a glucose-deficiency environment. Some researches show: a patient having overexpressed GRP78 has a higher recurrence rate no matter in what stage of cancer, and GRP78 overexpression makes cells of breast cancer have a higher chemotherapy resistance. This finding gives physicians a very important therapeutic reference. If GRP78 concentration is tested before chemotherapy, unnecessary medicine and useless therapy can be avoided. Besides, chemotherapy sensitivity can be promoted via reducing GRP78 expression.
Further, the Inventor found that GRP78 expression in head and neck cancer cells is much higher than the expression in non-cancer cells and that GRP78 expression correlates with clinical malignant indications, such as tumor size, tumor depth, lymph metastasis. Therefore, GRP78 expression can be used as a reference for tumor grading. However, in the current cancer therapeutic technology, neither molecular inhibition technology nor molecular therapeutic medicine is designed to effectively inhibit the expression of GRP78—the overexpressed gene in breast cancer/head and neck cancer.